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Drug discovery

Rules were made to be broken

Nature Reviews Chemistry volume 7, pages 3–4 (2023)Cite this article

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Twenty five years ago, Christopher Lipinski and colleagues published arguably the most influential sentence in small-molecule drug discovery. Their cleverly crafted ‘rule of 5’ (Ro5) mnemonic was adopted into everyday medicinal chemistry practice and has influenced a generation of small-molecule drug discovery scientists. Five times five years later, we consider the impact of the Ro5 and ask to what extent it should still guide today’s medicinal chemistry efforts.

Refers to Lipinski, C. A. et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Delivery Rev. 23, 3–25 (1997).

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Authors and Affiliations

  1. Discovery & Development Technologies, Merck HealthCare KGaA, Darmstadt, Germany

    Ingo V. Hartung

  2. Discovery & Development Technologies, EMD Serono, Inc., Billerica, MA, USA

    Bayard R. Huck & Alejandro Crespo

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  1. Ingo V. Hartung
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  2. Bayard R. Huck
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  3. Alejandro Crespo
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Correspondence to Ingo V. Hartung.

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Competing interests

I.V.H. is an employee of Merck Healthcare KGaA. B.R.H. and A.C. are employees of EMD Serono, Inc.

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Hartung, I.V., Huck, B.R. & Crespo, A. Rules were made to be broken. Nat Rev Chem 7, 3–4 (2023). https://doi.org/10.1038/s41570-022-00451-0

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